Somatic mutation as an explanation for epigenetic aging.

DNA methylation marks have recently been used to build models known as epigenetic clocks, which predict calendar age. As methylation of cytosine promotes C-to-T mutations, we hypothesized that the methylation changes observed with age should reflect the accrual of somatic mutations, and the two should yield analogous aging estimates. In an analysis of multimodal data from 9,331 human individuals, we found that CpG mutations indeed coincide with changes in methylation, not only at the mutated site but with pervasive remodeling of the methylome out to ±10 kilobases.

Subchondral insufficiency fracture of the knee.

Subchondral insufficiency fractures of the knee (SIFK) are a relatively common cause of knee pain, particularly in middle-aged and older adults. The SIFK is a type of stress fracture that occurs when excessive and repetitive or supraphysiologic loads are applied to subchondral bone [1]. Historically, this type of fracture was termed spontaneous osteonecrosis of the knee (SONK) until advances in MRI identified underlying fractures as well as meniscal deficiency as likely attributable etiologies.

Left atrial mechanics in youth with chronic kidney disease and similarly aged healthy controls.

Background: In adults with chronic kidney disease (CKD), abnormal left atrial reservoir strain (LASr) is an early, yet clinically significant, indicator of myocardial dysfunction. However, left atrial mechanics are understudied in youth with CKD. The objective of this study was to assess left atrial strain function in youth with CKD and similarly aged, healthy controls.

The integration of self-efficacy and response-efficacy in decision making.

The belief that we can exert an influence in our environment is dependent on distinct components of perceived control. Here, we investigate the neural representations that differentially code for self-efficacy (belief in successfully executing a behavior) and response-efficacy (belief that the behavior leads to an expected outcome) and how such signals may be integrated to inform decision-making. Participants provided confidence ratings related to executing a behavior (self-efficacy), and the potential for a rewarding outcome (response-efficacy).

Basal forebrain innervation of the amygdala: an anatomical and computational exploration.

Theta oscillations of the mammalian amygdala are associated with processing, encoding and retrieval of aversive memories. In the hippocampus, the power of the network theta oscillation is modulated by basal forebrain (BF) GABAergic projections. Here, we combine anatomical and computational approaches to investigate if similar BF projections to the amygdaloid complex provide an analogous modulation of local network activity.

High throughput method for simultaneous screening of membrane permeability and toxicity for discovery of new cryoprotective agents.

Cryoprotective agent (CPA) toxicity is the most limiting factor impeding cryopreservation of critically needed tissues and organs for transplantation and medical research. This limitation is in part due to the challenge of rapidly screening compounds to identify candidate molecules that are highly membrane permeable and non-toxic at high concentrations. Such a combination would facilitate rapid CPA permeation throughout the sample, enabling ice-free cryopreservation with minimal toxicity.

Morphology remodelling and membrane channel formation in synthetic cells via reconfigurable DNA nanorafts.

The shape of biological matter is central to cell function at different length scales and determines how cellular components recognize, interact and respond to one another. However, their shapes are often transient and hard to reprogramme. Here we construct a synthetic cell model composed of signal-responsive DNA nanorafts, biogenic pores and giant unilamellar vesicles (GUVs).

ERα dysfunction caused by ESR1 mutations and therapeutic pressure promotes lineage plasticity in ER breast cancer.

Multiple next-generation molecules targeting estrogen receptor α (ERα) are being investigated in breast cancer clinical trials, encompassing thousands of women globally. Development of these molecules was partly motivated by the discovery of resistance-associated mutations in ESR1 (encodes ERα). Here, we studied the impact of ERα antagonist/degraders against Esr1 mutations expressed in mouse mammary glands.

Assessing drywell designs for managed aquifer recharge via canals and repurposed wells.

This study explores innovative drywell designs for managed aquifer recharge (MAR) in agricultural settings, focusing on smaller diameter and deeper drywells, including the repurposing of dried or abandoned wells. Numerical simulations assessed the impact of drywell diameter (5-120 cm), depth (15-55 m), screen height, and subsurface heterogeneity on infiltration (I) and recharge (R) volumes over a one-year period under constant head conditions. Results indicate that smaller diameter drywells can effectively infiltrate and recharge significant water volumes.

Homologous recombination promotes non-immunogenic mitotic cell death upon DNA damage.

Double-strand breaks (DSBs) can initiate mitotic catastrophe, a complex oncosuppressive phenomenon characterized by cell death during or after cell division. Here we unveil how cell cycle-regulated DSB repair guides disparate cell death outcomes through single-cell analysis of extended live imaging. Following DSB induction in S or G2, passage of unresolved homologous recombination intermediates into mitosis promotes non-immunogenic intrinsic apoptosis in the immediate attempt at cell division.

Mind the leaf anatomy while taking ground truth with portable chlorophyll meters.

A wide range of portable chlorophyll meters are increasingly being used to measure leaf chlorophyll content as an indicator of plant performance, providing reference data for remote sensing studies. We tested the effect of leaf anatomy on the relationship between optical assessments of chlorophyll (Chl) against biochemically determined Chl content as a reference. Optical Chl assessments included measurements taken by four chlorophyll meters: three transmittance-based (SPAD-502, Dualex-4 Scientific, and MultispeQ 2.

Antisense mediated blockade of Dickkopf 1 attenuates tumor survival, metastases and bone damage in experimental osteosarcoma.

Osteosarcoma (OS) is the most common primary bone malignancy. The canonical Wnt inhibitor Dickkopf-1 (Dkk-1) has been implicated in bone destruction, tumor survival and metastases during OS. We examined the role of Dkk-1 in OS disease progression and explored strategies for targeting its activity.

A hydrothermal coupling model for permafrost subgrade considering temperature gradient and its application.

The thermodynamic properties of frozen soil depend on its temperature state and ice content. Additionally, the permeability coefficient significantly affects both the temperature distribution and water movement. In this study, the dynamic variation of soil permeability coefficient with temperature is considered, the permeability coefficient is defined as a piecewise function with temperature as independent variable, and the hydrothermal coupling equation is established.

Efficacy of melatonin treatment in a cystic fibrosis mouse model of airway infection.

Approaches to mitigate the severity of infections and of immune responses are still needed for the treatment of cystic fibrosis (CF) even with the success of highly effective modulator therapies. Previous studies identified reduced levels of melatonin in a CF mouse model related to circadian rhythm dysregulation. Melatonin is known to have immunomodulatory properties and it was hypothesized that treatment with melatonin would improve responses to bacterial infection in CF mice.

Influenza A virus in dairy cattle: infection biology and potential mammary gland-targeted vaccines.

Influenza, a major "One Health" threat, has gained heightened attention following recent reports of highly pathogenic avian influenza in dairy cattle and cow-to-human transmission in the USA. This review explores general aspects of influenza A virus (IAV) biology, its interactions with mammalian hosts, and discusses the key considerations for developing vaccines to prevent or curtail IAV infection in the bovine mammary gland and its spread through milk.

Action inflexibility and compulsive-like behavior accompany neurobiological alterations in the anterior orbitofrontal cortex and associated striatal nuclei.

The orbitofrontal cortex (OFC) is a large cortical structure, expansive across anterior-posterior axes. It is essential for flexibly updating learned behaviors, and paradoxically, also implicated in inflexible and compulsive-like behaviors. Here, we investigated mice bred to display inflexible reward-seeking behaviors that are insensitive to action consequences.

Assessing the impact of energy coaching with smart technology interventions to alleviate energy poverty.

Energy poverty affects 550,000 homes in the Netherlands yet policy interventions to alleviate this issue are rare. Therefore, we test two energy coaching interventions in Amsterdam: a static information group (n = 67) which received energy efficient products and one energy-use report, and a smart information group (n = 50), which also had a display providing real-time feedback on energy-use. Results across both groups, show a 75% success rate for alleviating energy poverty.

A broad spectrum Shigella vaccine based on VirG multiepitope region produced in a cell-free system.

Dysentery caused by Shigella species remains a major health threat to children in low- and middle-income countries. There is no vaccine available. The most advanced candidates, i.

Language style (mis)matching: Consuming entertainment media from someone unlike you is linked to positive attitudes.

Prior work suggests people often match with conversational partners by using a common rate of style words (e.g., articles, pronouns).

Regulation of stress granule maturation and dynamics by poly(ADP-ribose) interaction with PARP13.

Non-covalent interactions of poly(ADP-ribose) (PAR) facilitate condensate formation, yet the impact of these interactions on condensate properties remains unclear. Here, we demonstrate that PAR-mediated interactions through PARP13, specifically the PARP13.2 isoform, are essential for modulating the dynamics of stress granules-a class of cytoplasmic condensates that form upon stress, including types frequently observed in cancers.

Artificial intelligence-enhanced diagnosis of degenerative joint disease using temporomandibular joint panoramic radiography and joint noise data.

This study aimed to develop an artificial intelligence (AI) model for the screening of degenerative joint disease (DJD) using temporomandibular joint (TMJ) panoramic radiography and joint noise data. A total of 2631 TMJ panoramic images were collected, resulting in a final dataset of 3908 images (2127 normal (N) and 1781 DJD (D)) after excluding indeterminate cases and errors. AI models using GoogleNet were evaluated with six different combinations of image data, clinician-detected crepitus, and patient-reported joint noise.

Involvement of p38 MAPK and MAPKAPK2 in promoting cell death and the inflammatory response to ischemic stress associated with necrotic glioblastoma.

The association of necrosis in tumors with poor prognosis implies a potential tumor-promoting role. However, the mechanisms underlying cell death in this context and how damaged tissue contributes to tumor progression remain unclear. Here, we identified p38 mitogen-activated protein kinases (p38 MAPK, a.

Dysregulated autoantibodies targeting AGTR1 are associated with the accumulation of COVID-19 symptoms.

Coronavirus disease 2019 (COVID-19) presents a wide spectrum of symptoms, the causes of which remain poorly understood. This study explored the associations between autoantibodies (AABs), particularly those targeting G protein-coupled receptors (GPCRs) and renin‒angiotensin system (RAS) molecules, and the clinical manifestations of COVID-19. Using a cross-sectional analysis of 244 individuals, we applied multivariate analysis of variance, principal component analysis, and multinomial regression to examine the relationships between AAB levels and key symptoms.